Induction of CNS inflammatory disease as a consequence of CTLA-4/B7 blockade

We and others have shown that CTLA-4/B7 interactions participate in the regulation of experimental autoimmune encephalomyelitis(EAE). Blockade of CTLA-4/B7 interactions results in an exacerbated clinical and histopathological disease course in susceptible SJL mice. Here we show that blockade of CTLA-4 signaling allows induction of EAE in non-susceptible mice (BALB/C) immunized with mouse spinal cord homogenate. This disease course is marked by severe mononuclear cell infiltration into the central nervous system. Preliminary evidence also suggests that interruption of CTLA-4 signals enhances T cell activation that results in clinical and histopathologic disease in animals sensitized to a myelin-associated peptide known to induce a proliferative response in BALB/C mice but not clinical disease. These results implicate CTLA-4 signals as critical to the regulation of potentially autoreactive peripheral T cells.